Selective Antagonism of the ET_A Receptor, but Not the ET_B Receptor, Is Protective Against Ischemic Acute Renal Failure in Rats

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Author(s)

Abstract

We investigated the effects of ABT-627, a selective ET<SUB>A</SUB>-receptor antagonist, and A-192621, a selective ET<SUB>B</SUB>-receptor antagonist, on ischemic acute renal failure(ARF)in rats.Ischemic ARF was induced by clamping the left renal artery and vein for 45min, 2 weeks after the contralateral nephrectomy.Renal function in untreated ARF rats markedly decreased at 24h after reperfusion and thereafter tended to recover gradually.ABT-627(1mg/kg, i.v.)administration before ischemia markedly attenuated the renal dysfunction induced by the ischemia/reperfusion, whereas A-192621(3mg/kg, i.v.)pretreatment was without effect.Histopathological examination of the kidney of untreated ARF rats revealed severe renal damage such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion.Histologically evident damage was improved by pretreatment with ABT-627, but not with A-192621.Daily oral administration of ABT-627(10mg/kg per day), but not A-192621(30mg/kg per day), given after the ischemia/reperfusion period also exerted protective effects.These findings clearly indicate that endothelin, acting via the ET<SUB>A</SUB> receptor, participates in the pathogenesis of ischemic ARF.Thus, selective ET<SUB>A</SUB>-receptor antagonism may be useful in the treatment of human ischemic ARF, whereas selective blockade of the ET<SUB>B</SUB> receptor will probably be ineffective.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 82(4), 307-316, 2000-04-01

    The Japanese Pharmacological Society

References:  37

Cited by:  7

Codes

  • NII Article ID (NAID)
    10008183860
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    5362759
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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